We are following a diverse cohort of volunteer women from throughout the US and Puerto Rico between the ages of 35 and 74 who have a sister with breast cancer but did not have breast cancer themselves when they joined the study. At enrollment, data on potential risk factors and current health status were collected using computer assisted telephone interviews and mailed questionnaires. Blood, urine, and environmental samples were collected in a home visit and banked for future use in nested studies of women who develop breast cancer (or other diseases) and a sample of those who don't. The cohort is tracked annually for changes in vital status and major health outcomes. Detailed follow-up questionnaires on health outcomes, environmental and lifestyle exposures, and special topics are completed every 2-3 years. Medical records and tumor tissue (for breast cancer cases) are retrieved for those who develop cancer or other conditions of interest. The cohort was enrolled between 2003 and 2009. Nearly 51,000 women completed all baseline study activities. The response rates for annual updates range from 90-98%. The first Sister Study Biennial follow-up survey was completed in June 2012; responses were obtained from 48,090 women for a response rate of 95%. With the next round of detailed follow-up, which began in January 2012, the study has shifted to triennial administration to reduce participant burden and simplify workflow. Triennial questionnaires have been collected from over 20,000 eligible women to date. More than 1,800 women have reported a diagnosis of breast cancer or DCIS/LCIS; medical records and tumor tissue are being sought for those 6 months post diagnosis. Medical records are also sought for women reporting other cancer types, over 1,600 women to date. In April 2012 the Sister Study Scientific Advisory Board convened to help prioritize a long-term research strategy for addressing questions related to the role of environment and genes in breast cancer. At the Boards suggestion, the Sister Study is assembling a working group to evaluate chemicals of current interest and suitable measurement techniques. Research studies using baseline and follow-up data are exploring risk factors for breast cancer and other health conditions. Recent papers have examined eating patterns and sleep duration, employment and work schedule and telomere length, lifestyle behaviors in black and white women, accuracy and reliability of self-reported weight and height, early life factors in relation to uterine leiomyomata in black women, and early life factors and the risk of rheumatoid arthritis in adulthood. Using data from a case-cohort study involving the first 350 breast cancer cases and a sample of 700 women selected from the cohort, we completed an analysis of telomere length in peripheral blood and breast cancer risk, finding no association in our prospectively collected data. In a study of urinary prostaglandin E2-metabolite (PGE-M) and breast cancer risk in 609 (301 cases and 308 subcohort members) postmenopausal women, several known pro- and anti-inflammatory factors were associated with urinary PGE-M, and post-menopausal breast cancer risk was increased with increasing levels of urinary PGE-M among women who did not regularly use non-steroidal anti-inflammatory drugs (NSAIDs). These results support a role for prostaglandin E2 and inflammation in breast carcinogenesis, which may be modifiable by lifestyle and pharmacological interventions. Analyses are underway for a validation study of over 1,800 participants and their mothers aimed at evaluating how accurately women reported the information on early life collected at baseline, including information on their mothers pregnancy. Preliminary results comparing mothers and daughters responses suggest moderate or better agreement for most of the factors studied. Other studies in progress include early life factors and telomere length in peripheral blood as well as in relation to age at menarche, and analyses examining several factors in relation to breast cancer risk including genetic variants, occupational organic solvent exposure, adiposity, and antibiotic use. A series of analyses are examining DNA global and gene-specific methylation in relation to exposures such as diethylstilbestrol in utero and physical activity throughout the lifetime, as well as in relation to breast cancer risk. Results of several analyses have been presented at national scientific meetings and manuscripts are in preparation for publication. With co-investigators at the University of Washington, the Sister Study completed geocoding participant addresses, allowing attainment of environmental exposure data near participant residences such as current and historical air pollution measurements. A study of exposure to residential air pollution and blood pressure is in progress. Future plans include the development of a comprehensive statistical framework for assessing the health effects of exposure to multi-pollutant mixtures of pollutants, as well as the study of air and other pollutants and the risk of asthma and breast cancer. The Sister Study is conducting breast cancer survivor research with a group from the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention (CDC), headed by Dr. Mary White, Chief, Epidemiology and Applied Research Branch. This effort is funded in part by the Young Women's Breast Health Awareness and Support of Young Women Diagnosed with Breast Cancer bill, a 2010 congressional bill also known as the EARLY Act. A workshop of experts was held in January 2011 on state-of-the-art breast cancer survivorship research, resulting in recommendations on how the Sister Study can best contribute to this area of research. This collaboration has involved the development and administration of two special surveys. The first, completed in April 2012, covered breast cancer screening practices, family communication about cancer, and the effect of having a sister with breast cancer participants and their families; responses were collected from 20,000 women and data analysis is in progress. The second survey, currently in development, is for women diagnosed with breast cancer and includes topics that are of particular interest to younger women such as body image, work-life balance, relationships and intimacy, and fertility. Together, these surveys will increase our understanding of the impact of cancer in the lives of breast cancer survivors and their families and provide information on survivors quality of life, physical and emotional health, changes in lifestyle and environment, and coordination of cancer treatment and follow-up care that will help identify factors related to healthy living after diagnosis. The Sister Study participates in the National Cancer Institutes Cohort Consortium, a group that facilitates the pooling of data from individual cohort studies to create databases large enough to investigate risk factors for rare cancers. The Sister Study is contributing to Cohort Consortium studies on head and neck, gallbladder and ovarian cancers, allowing it to contribute to research it could not address on its own. The Sister Study is also a member of the International Harmonization Initiative (McGill University, Montreal), an international effort that aims to harmonize data collected across different studies in order to enable collaborative research using large, high-quality databases. A related study known as the Two Sister Study completed enrollment in December 2010. This family-based study on environmental and genetic risk factors for young onset breast cancer builds on the Sister Study by recruiting the participant's sister with breast cancer and parents who were asked to provide a saliva sample for a source of DNA, see Weinberg Z01-ES044005.